Results Of The DFCI ALL Consortium Protocol 05-001 For Children and Adolescents With Newly Diagnosed ALL

• Published in: Blood 2013-11, Vol.122 (21), p.838-838
• Main Authors: Silverman, Lewis B., Stevenson, Kristen E., Athale, Uma H., Clavell, Luis A., Cole, Peter, Kelly, Kara A., Leclerc, Jean-Marie, Michon, Bruno, Schorin, Marshall A., Schwartz, Cindy L, Asselin, Barbara, Supko, Jeffrey G, Hunt, Sarah, Andrew, Place, Vrooman, Lynda M., Neuberg, Donna S., Sallan, Stephen E.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V122.21.838.838

Current treatment regimens for childhood ALL have resulted in long-term event-free survival (EFS) of approximately 80%. On DFCI ALL Consortium Protocol 05-001, patients (pts) with newly diagnosed ALL aged 1-18 years (yrs) who achieved complete remission (CR) were eligible to participate in a randomized comparison of native E.coli asparaginase (ASP) given intramuscularly (IM) and PEG ASP, the polyethylene glycol conjugate of E.coli ASP, given intravenously (IV). The objective was to compare the serum ASP activity (SAA), toxicity, and EFS of the two ASP preparations. An intensified consolidation regimen for VHR pts, including B-ALL pts with high end-induction minimal residual disease (MRD), was also evaluated. All pts received 1 dose of PEG ASP (2500 IU/m2) during the 4-week (wk) multiagent induction phase. After CR was achieved, final risk group was assigned based on age, presenting WBC, CNS status, cytogenetics and end-induction MRD (assessed by PCR). All T-ALL pts were considered HR. Pts were considered VHR if they met one of the following criteria: i) B-ALL with high end-induction MRD; or ii) adverse cytogenetics (MLL gene rearrangement or hypodiploidy). BCR-ABL positive pts began daily imatinib at Day 18 and were allocated to allogeneic transplant in 1st CR. Beginning at wk 7, pts began the consolidation phase including 30 wks of ASP, either IM E.coli ASP 25000 IU/m2 weekly or IV PEG 2500 IU/m2 every 2 wks. In addition, SR pts received every 3-wk cycles with vincristine, dexamethasone, 6MP and low-dose methotrexate (mtx) during consolidation; HR pts received doxorubicin (cumulative dose 300 mg/m2) with dexrazoxane instead of mtx during this phase. VHR pts received 2 additional cycles beginning at week 7 (cyclophosphamide/low-dose araC/6-MP and then high-dose araC/etoposide/dexamethasone), followed by the HR consolidation phase. Continuation phase was identical for all pts. Total duration of therapy was 25 months. Serum samples were obtained every 6 wks just prior to an ASP dose to measure SAA. EFS rates were calculated from date of registration, except for EFS by randomized arm, risk group, and end-induction MRD, which were calculated from time of randomization. Between 2005-2010, 551 evaluable pts enrolled, of whom 526 (95%) achieved CR. 463 pts participated in the ASP randomization. Median nadir SAA was significantly higher with IV PEG than with IM E.coli ASP,(Table 1) with more IV PEG-randomized pts achieving nadir SAA ≥ 0.1 IU/mL (p